Abstract

Introduction:
Dressler Syndrome should be considered in the differential diagnosis of chest pain, especially in patients who are in a late stage of the evolution of the ischemic process.

Case Presentation:
A 46-year-old male was admitted to the emergency department due to pleuritic chest pain. Two weeks before this admission, he presented with a typical angina episode, likely an ST segment elevation myocardial infarction (STEMI), and did not receive reperfusion therapy or any medical care. The patient’s electrocardiogram showed diffuse ST segment elevation and PR segment depression, and his blood tests showed positive myocardial necrosis markers. A coronary angiography showed a proximal occlusion (not recanalized) of the circumflex artery. There was a late gadolinium enhancement area seen through cardiac magnetic resonance imaging (CMR), suggestive of recent transmural infarction, pericardial injury, and pleural effusion (inflammatory).

Conclusions:
These findings strongly suggest the diagnosis of delayed post-infarction pericarditis, or Dressler Syndrome, a rare disease in the age of reperfusion therapy. Although rare, it is a syndrome that must be considered in the differential diagnosis of chest pain.

1. Introduction

Dressler syndrome (DS) was first described by William Dressler in 1956, after observing the late period development of an acute myocardial infarction (1). It is an immuno-inflammatory disease similar to others that occur after myocardial injury, such as post-pericardiectomy syndrome and post-traumatic pericarditis (2). After myocardial infarction (MI), injuries to the cardiac myocytes expose myocardial antigens to the immune system, stimulating immune complex formation. This immune system activation triggers a systemic immune-inflammatory response that may involve other organs, such as the pleura, due to immune cross-reactions (3). The symptoms tend to occur 2 - 3 weeks after MI, and may include pleuritic chest pain and fever. A direct relationship between systemic inflammation and myocardial ischemia has been demonstrated by several authors (2, 3).

2. Case Presentation

A 46-year-old male with hypertension and diabetes had a 30-minute long episode of strong oppressive chest pain during physical exertion, radiating to the jaw, but did not seek medical care. Two weeks later, the patient came to the emergency department of the heart institute (InCor) at the University of Sao Paulo, Brazil, in January of 2015, reporting pain of a different pattern: severe constrictive chest pain lasting one hour that worsened with deep inspiration and while in a supine position. The physical examination demonstrated a blood pressure of 140/85 mmHg (semi-automatic digital sphygmomanometer, Omron 705CP, calibrated), tachycardia (105 bpm), temperature of 99.5°F, and no jugular venous distension. A pericardial friction sound was easily audible at the lower left sternal border. Moreover, the electrocardiogram (EKG Machine, Philips PageWriter Trim III, calibrated) showed diffuse ST-segment elevation with a depression of the PR segment, mainly in DII (Figure 1), highly suggestive of pericarditis. Chest radiography showed a cardiac area in the upper normal limit, and mild right pleural effusion. The results of the laboratory blood tests were as follows: glucose = 307 mg/dl, CKMB = 5.8 ng/mL (normal = < 4 ng/mL), troponin I = 18 ng/mL (normal = < 1.0 ng/mL), Hb = 15.2 g/l, WBC = 8,600/µL (no predominance of younger lineages), and platelets = 162,000. The lipid profile was normal, the myocardial necrosis markers decreased progressively during an in-hospital stay, and the echocardiogram (GE Vivid 7) demonstrated inferolateral hypokinesia, with a left ventricle ejection fraction (LVEF) of 0.55, without pericardial effusion. The clinical characteristics are described in Table 1.

The coronary angiography revealed proximal occlusion of the circumflex artery, without other stenosis, and an angioplasty attempt was unsuccessful due to the impossibility of overcoming the obstruction. Cardiac magnetic resonance imaging (CMR) was performed to analyze the pericardium, and to better characterize the extent of the ischemia. A transmural inferolateral late gadolinium enhancement was found, suggestive of fibrosis due to myocardial infarction (MI) (Figure 2A), with an underlying area of no-reflow (microvascular obstruction, indicating a recent injury), inferior akinesia (LVEF = 0.34), pericardial injury (a small area of epicardial scarring in the left lateral wall), and mild right pleural effusion (Figure 2B). A semiautomatic quantification of fibrosis determined a 7.6 g myocardial scar (8% of the total myocardial volume) by that time (3 standard deviations and full width at half maximum, Circle CVI Software, version 4.2.1).

The clinical features of the patient’s chest pain (different from the initial pain two weeks before), and the highly suggestive electrocardiogram and CMR findings suggest late post MI pericarditis or Dressler Syndrome. The patient received full anti-ischemic drug treatment, in addition to aspirin at an anti-inflammatory dose of 2 g/day, and exhibited improvement in his chest pain. He was then discharged on the fourth day of hospitalization.

3. Discussion

A young patient (46-year-old) with hypertension and diabetes was admitted to the emergency department complaining of chest pain. The presence of constrictive chest pain in a patient with coronary artery disease risk factors initially suggested acute myocardial ischemia. However, the worsening of the chest pain upon deep breathing and while in a supine position, in addition to a clear pericardial friction sound, could also indicate pericarditis. In the clinical history, the patient had an initial complaint of typical angina two weeks previously, followed by the actual pleuritic chest pain which led him to our emergency department. The electrocardiogram, demonstrating diffuse ST-segment elevation and depression of the PR, was highly suggestive of pericarditis. In some cases, PR segment depression can occur even in the absence of ST-segment elevation, and may appear as the initial manifestation of acute pericarditis (4).

The elevation of the myocardial necrosis markers may indicate coronary ischemia or the myopericardial pathological process known as myopericarditis. Patients with acute coronary syndrome who develop great elevations in their myocardial necrosis markers, especially without reperfusion therapy (as in this case), are at a higher risk of developing post-infarction pericarditis (5).

Interestingly, the markers collected upon admission showed the typical kinetics of a subacute process of about 2 weeks: the CKMB was almost normal (5.8 ng/mL) and the troponin, although still very high (18 ng/mL), was also reducing progressively. The echocardiogram showed no evidence of pericardial effusion, which is not mandatory for the diagnosis of pericarditis. However, the evidence of persistent chest pain, elevated myocardial necrosis blood markers, and inferolateral hypokinesia without pericardial abnormalities, led to an early coronary angiography, which detected a proximal occlusion of the circumflex artery without the features of acute thrombosis. The suspicion of persistent ischemia motivated an attempt to perform angioplasty, which was not possible due to the inability to overcome the obstruction, reinforcing the hypothesis of a chronic or subacute injury to that coronary site. The patient underwent a CMR to further determine the ischemia burden, and for a better evaluation of the pericardium (6). Confirming the clinical hypothesis, the CMR images showed inferolateral transmural necrosis (with features of subacute evolution), subtle pericardial involvement (but with no effusion), and evident right pleural effusion, which is an inflammatory signal described in DS (Figure 2B). The patient’s history, laboratory, and imaging findings led to the hypothesis of an acute MI without reperfusion therapy two weeks before his visit to the emergency department, which was complicated by late pericarditis, strongly suggesting the possibility of DS. In the case described, the immuno-inflammatory response was suggested by the presence of pleural effusion, similar to other descriptions of the clinical presentation of DS (7), correctly evidenced by the CMR (Figure 2B).

There was an interval of two weeks between the typical angina (probably related to the MI) and the new chest pain with characteristics of pericardial involvement. The diagnosis of DS requires the occurrence of pericardial injury in the subacute post-MI period. In a study of 15 cases with characteristics of DS, the clinical presentation of pleuritic pain occurred up to the 21st day after the MI in 66.7% of the patients (8).

Before the era of reperfusion, DS occurred after about 1% - 5% of the reported MIs; however, the incidence of DS has declined dramatically, either after the advent of fibrinolysis (9) or after the spread of percutaneous reperfusion treatment. A prospective study of 201 patients with acute MIs undergoing thrombolytic therapy did not detect the onset of DS in any patient undergoing early reperfusion (5). Based on this finding, it was postulated that the decrease in the infarct size promoted by the early coronary reperfusion, and the shorter exposure of the immune system to the myocardial antigens, promoted the virtual disappearance of this entity (10, 11).

This case highlights the importance of the clinical assessment of patients admitted with chest pain. Although rare, Dressler Syndrome should be considered in the differential diagnosis of chest pain, especially in patients who are in a late stage of the evolution of the ischemic process. This becomes especially important in developing countries, where many patients receive no reperfusion therapy due to difficulties in accessing the healthcare system.

Acknowledgements

The authors would like to thank Valeria Costa Hong for her guidance in the organization of the references.